Promising Efficacy and Safety Demonstrated With Envafolimab, Lenvatinib, and TACE in Unresectable HCC

Findings from the phase 2 CISLC-12 study (NCT05213221) show favorable safety and efficacy signals for patients with unresectable hepatocellular carcinoma (HCC) treated with the combination of envafolimab (KNO35), lenvatinib (Lenvima), and transarterial chemoembolization (TACE). Data were presented during the 2023 Gastrointestinal Cancers Symposium^.1

With a primary end point of objective response rate (ORR), results showed that patients (n = 36) achieved an ORR of 36.1% with 0 complete responses per RECIST 1.1 criteria. Outcomes assessed using modified RECIST (mRECIST) criteria showed an ORR of 77.8% with 1 complete response.¹

Investigators reported that 11 patients received radical resection after a conversion from unresectable HCC to resectable disease.

“Envafolimab combined with lenvatinib plus TACE yielded favorable efficacy and safety outcomes, representing a promising therapeutic modality for patients with [Barcelona clinic liver cancer] BCLC B/C unresectable HCC,” wrote the authors in a poster of the data.

Patients enrolled had BCLC stage B (47.2%) or C (52.8%) unresectable HCC. Among 40 patients in the safety population, no treatment-related deaths occurred. The most common adverse events (AEs) were aspartate aminotransferase (AST) increase (75.0%), alanine transaminase (ALT) increase (65.0%), decreased white blood cell count (42.5%), gastrointestinal bleeding (42.5%), decreased platelet count (40.0%), increased blood thyroid stimulating hormone (37.5%), decreased neutrophil count (37.5%), and hypoalbuminemia (22.5%).¹

There was 1 grade 4 AE reported for each of the following events: increase in AST, increase in ALT, and gastrointestinal bleeding. Grade 3 AEs included increase in AST (n = 13), increase in ALT (n = 7), decrease in platelet count (n = 7), and decreased neutrophil count (n = 1).

Based on RECIST 1.1 and mRECIST, patients achieved a DCR of 77.8% vs 80.6%, a stable disease rate of 41.7% vs 2.8%. Progressive disease was reported in 19.4% vs 16.7% of patients using RECIST and mRECIST criteria, respectively. Survival data are not mature yet.¹

The agents were given for up to 2 years or until disease progression or unacceptable toxicity. Lenvatinib was given at 8 mg at day to patients under 60 kg and at 12 mg a day for patients 60 kg or more and envafolimab was given as a 300 mg subcutaneous injection once every 3 weeks. TACE occurred every 6 weeks based on the proportion of viable tumors according to investigators’ consideration and an imaging evaluation was conducted every 6 weeks.2 Secondary end points were disease control rate (DCR), duration of response, progression-free survival, overall survival, and safety.¹

The prospective, open-label, single-arm study performed at the First Affiliated Hospital at Zhejiang University in China enrolled patients from March 2022 to September 2022 and is actively recruiting. The median age of patients enrolled was 54.5 years (range, 18-75), 5.6% were metastatic, Child–Pugh scores were either 5 (94.4%) or 6 (5.6%), and patients had portal vein tumor thrombosis as well as hepatic vein tumor thrombus at rates of 36.1% and 5.6%, respectively. All patients had ECOG performance score of 0, at least 1 measurable lesion, and did not receive prior systemic chemotherapy.¹

As TACE is a standard treatment for patients with intermediate-stage HCC and lenvatinib has shown efficacy when combined with immune checkpoint inhibitors in the treatment of HCC, investigators continue to evaluate the combination of therapies with the anti–PD-L1 inhibitor envafolimab.

Previously, a retrospective controlled study showed that patients (n = 60) treated with lenvatinib and TACE achieved an ORR of 68.3% compared with 31.7% for patients who received TACE alone as assessed by mRECIST (P < .001). The DCR was 93.3% vs 86.7%, (P = .224), respectively, and the most common AEs with the combination treatment were decreased albumin (55.0%), hypertension (48.3%) and decreased platelet count (46.7%).³

References

1. Chen Y, Huang X, Hu W, et al. Efficacy and safety of envafolimab plus lenvatinib combined with TACE in unresectable hepatocellular carcinoma: An open-label, single-arm, phase 2 study—the CISLD-12 study. J Clin Oncol. 2023;41(suppl 4):558. doi:10.1200/JCO.2023.41.3_suppl.558
2. Study on therapeutic effect of combination of envafolimab, Lenavatinib and TACE in advanced HCC patients (CISLD-12). ClinicalTrials.gov. Updated March 15, 2022. Accessed January 20, 2023. https://clinicaltrials.gov/ct2/show/NCT05213221
3. Fu Z, Li X, Zhong J, et al. Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study. Hepatol Int. 2021;15(3):663-675. doi:10.1007/s12072-021-10184-9